Genetics of endometriosis-associated ovarian cancer: A systematic review

Up to 1.6% of patients with endometriosis develop epithelial ovarian carcinoma. The genetic overlap between endometriosis and ovarian cancer has not been fully characterized. This review aims to describe the current literature on mutations correlated with endometriosis-associated epithelial ovarian carcinoma.

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO ID: CRD42023400697), Cochrane Library, Embase, PubMed, Scopus, and Web of Science Core Collection databases were queried from January 1st, 1995, to April 1st, 2022 for English language studies on the genetic basis of endometriosis-associated epithelial ovarian carcinoma. The quality of included studies was assessed using the Newcastle-Ottawa Scale.

Search criteria yielded 18,639 articles, of which 30 met inclusion criteria. 70 genes were assessed in the 30 included studies, and 9 of these appeared in two or more studies. The most frequently mutated genes were PIK3CA, PTEN, ARID1A and CTNNB1. None of these genes had a mutation frequency greater than 0.5 when data from all 30 studies were aggregated. Stratification by epithelial ovarian cancer subtype revealed an association between CTNNB1 mutation and endometrioid carcinoma (47/97; 48.4%) compared to clear cell carcinoma (4/38; 10.5%) (p = 0.00004).

Due to the low mutation frequency of commonly studied genes, cumulative mutational burden may better explain the progression and pathogenesis of endometriosis-associated epithelial ovarian carcinoma than any single mutation. CTNNB1 may be associated with the development of endometrioid ovarian carcinoma. Future studies may consider the use of polygenic scores for risk assessment of endometriosis-associated ovarian cancer.